tbuckley/cabot-search huggingface dataset:
GCT-11. 24 Gy whole ventricular radiotherapy alone is sufficient for disease control in localised germinoma in CR after initial chemotherapy – final of the SIOP CNS GCT II study
Authors: Gabriele Calaminus, Brigitte Bison, Cecile Faure Conter, Didier Frappaz, Andreas Peyrl, Nicolas U Gerber, Jans-Enno Müller, Thankamma Ajithkumar, Giovanni Morana, Justin Cross, Torsten Pietsch, Colin Smith, Kristin Solem, Irenne Devenney, Maria Luisa Garre, Herve Brisse, Martin Zimmermann, Rolf-Dieter Kortmann, Claire Alapetite, James Nicholson
Journal: Neuro-Oncology (2022)

Abstract SIOP CNS GCT II aimed to establish if 24 Gy Whole Ventricular Radiotherapy (WVRT) in localised germinoma is sufficient for tumour control. After central review of radiological response after ‘CarboPEI’ chemotherapy, patients in complete remission (CR) were consolidated with 24 Gy WVRT. Between 2/2012 and 7/2018, 194 patients from 8 European countries with histologically-confirmed fully-staged localised germinoma were registered, of whom 167 were protocol pts. CR after chemotherapy was achieved in 65 patients, Of the 102 patients not in CR after chemotherapy 91 had partial remission (PR), 8 stable disease (SD), 3 progressive disease (PD). All 65 patients in CR received 24 Gy WVRT alone; two of these relapsed, both locally, 7 and 12 months after diagnosis. Of the 102 non-CR patients after chemotherapy, 91 with PR and 8 with SD received 24 Gy WVRT and 16 Gy boost, of which five relapsed (four local, one distant) 2 -7 years from diagnosis. One additional patient who remained in CR died of infection in CR, 4 years after Dx. In three patients with PD all received 24 Gy ventricular irradiation with varying tumour boosts. 16-30 Gy, no relapses occurred. Median follow-up of the whole group was 4,2 years. 4- years event-free survival (EFS) for patients in CR treated with WVRT only (n=65) was 97% (standard error 2%). 4-years EFS for patients with non-CR ( WVRT 24 Gy and 16 Gy to 30 Gy tumour boost) (n=102) was 95% (standard error 2%). Localised germinoma in CR after chemotherapy had an excellent outcome with 24 Gy WVRT alone. 24 Gy WVRT is therefore considered the standard consolidation treatment in this group and should be used as the standard for further treatment studies in localised germinoma evaluating the recent international consensus on radiological response criteria ( Lancet Oncology accepted).
Real-world cost for first-line treatment for prostate cancer: A comparative cost analysis in the public sector
Authors: S. Reddy, B. Hanna, R. Ferguson, S.R. Jackson, H. Rose, D. Chia, M. Azzi, R. Ko, M. Winter, M. Arianayagam, B. Canagasingham, A. Goolam, N. Jeffery, N. Mehan, C. Varol
Journal: European Urology (2022)
Circulating tumor DNA and recurrence risk in stage II-III gastric cancer.
Authors: Shu-Qiang Yuan, You-Sheng Huang, Run-Cong Nie, Yingbo Chen, Si-Yu Wang, Xiaowei Sun, Yuanfang Li, Ze-Kun Liu, Yan-Xing Chen, Yi-Chen Yao, Yu Xu, Haibo Qiu, Yao Liang, Wei Wang, Zhiwei Zhou, Rui-hua Xu, Feng Wang
Journal: Journal of Clinical Oncology (2022)

4054 Background: Circulating tumor DNA (ctDNA) is a promising biomarker for detecting molecular residual disease (MRD) and relapse after definitive treatment in multiple solid cancers. However, the significance of ctDNA is rarely clarified in locoregional gastric cancer (GC). Here, we conducted a prospective and observational study to evaluate the utility of ctDNA in predicting the recurrence risk of GC. Methods: From October 2016 to June 2019, 100 patients with stage II/III resectable GC were recruited in this study (NCT02887612). Primary tumors and plasma samples were collected perioperatively and after adjuvant chemotherapy (ACT). Somatic variants were captured via a targeted sequencing panel of 425 cancer-related genes. The plasma of patients was defined as ctDNA positive only if one or more variants detected in the plasma presented in at least 2% of the primary tumors. All the patients received curative-intent standard-of-care therapy. Results: Preoperative ctDNA was detectable in 38 (38.0%) patients but showed limited value for predicting recurrence. After surgery (median days, 4), the plasma of 25 (25.0%) patients were still ctDNA positive and they had higher recurrence risk than the non-positive patients (hazard ratio [HR], 2.74 (95% CI: 1.37–5.48); P = 0.003). Forty-one patients had evaluable plasma after ACT and 10 (24.4%) of them who were ctDNA positive had remarkably higher recurrence and death risk compared with ctDNA-negative patients (recurrence-free survival [RFS] HR = 14.99 (95% CI: 3.08–72.96); P &lt; 0.001; overall survival HR, 11.88 (95% CI: 2.38–59.24); P &lt; 0.001). In particular, post-ACT ctDNA achieved better predictive performance (sensitivity, 77.8%; specificity, 90.6%) than both postoperative ctDNA and post-treatment tumor biomarkers (i.e., CEA, CA199, and CA72-4). In all multivariate analyses, ctDNA positivity was an independent factor of RFS. Patients with ERBB4 mutation in their primary tumors had poorer RFS compared to those were ERBB4 wildtype (HR = 3.46 (95% CI: 1.32–9.03); P = 0.007). A comprehensive model incorporating ctDNA status for recurrence risk prediction showed a higher concordance index (0.78; 95%CI, 0.71–0.84) than the model without ctDNA status (0.71; 95%CI, 0.64–0.79; P = 0.009). Conclusions: Postoperative and post-ACT ctDNA was associated with MRD and high risk of relapse in patients with stage II/III GC and can be utilized to guide GC management in post-surgical settings.
Duration of follow-up and timing of discharge in adult patients with urolithiasis after surgical or medical intervention: A systematic review and meta-analysis from the European Association of Urology Guideline Panel on Urolithiasis
Authors: L. Tzelves, R. Geraghty, R. Lombardo, N.D. Davis, A. Neisius, A. Petřík, G. Gambaro, C. Türk, K. Thomas, B. Somani, A. Skolarikos
Journal: European Urology (2022)
Myocardial tissue slices for modeling of the human PLN p.Arg14del associated cardiomyopathy
Authors: JSA Van Der Geest, Z Lei, PAFM Doevendans, JPG Sluijter
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NWO - The Dutch Research Council Background Current in vivo preclinical models lack the predictability of the clinical efficacy resulting in a high dropout rate of therapeutic candidates. Advanced human-based models are required to bridge this gap and indicate the potential of novel therapeutic approaches[1]. Myocardial tissue slices are an in vitro model that recapitulates the native multicellular architecture of the heart. This allows for modeling cellular processes in a macroscopic context entailing great promise. The most common cardiomyopathy-related mutation in the Netherlands is the loss of arginine at position 14 (p.Arg14del) in the phospholamban protein (PLN). PLN is a critical regulator of calcium cycling and contractility in the heart. The p.Arg14del mutation results in a super inhibition of SERCA2a and thus aberrant calcium handling and reduced contractile force. Mice models harbouring the PLN p.Arg14del do not completely recapitulate the human manifestation mainly due to the difference between species; heart rate, Calcium-cycling and ion properties, and different myosin heavy chain isoforms, showing the unmet need for a human-based model[2,3]. Methods &amp; Results 300 µm thick viable myocardial tissue were sectioned from a PLN p.Arg14del patient’s left ventricle. Although the myocardial tissue slices were kept alive for eight days in static culture, these conditions initiated cell death and dedifferentiation. The tissue slices show the greatest resemblance to the intact architecture of the in vivo human heart, it is the most relevant model for viral transduction in the human heart, and proof-of-principle of this is performed. Myocardial tissue slices of a PLN p.Arg14del patient retain the structural phenotype shown by the fibrofatty deposition. Similarly, functional patient characteristics, aberrant calcium handling, and reduced contractile force are preserved. Conclusion Myocardial tissue slices recapitulate the (patho)physiology of the heart, as shown here with the PLN p.Arg14del case. However, the static culture conditions induce remodeling of the heart and thus only allow for acute measures in the native heart. To prolong the period that the slices recapitulate the native heart, culture conditions should mimic the environment of the heart. The tissue slices allow for a currently unmet need to modulate the complex architecture of the human heart with e.g. novel delivery tools or therapeutic interventions. All in all, myocardial tissue slices are a promising model that can give novel insights into the physiology of the human heart, and therapeutic intervention on induced or genetic cardiomyopathies.
Fecal microbiota and bile acids in IBD patients undergoing screening for colorectal cancer
Authors: Aonghus Lavelle, Stéphane Nancey, Jean-Marie Reimund, David Laharie, Philippe Marteau, Xavier Treton, Matthieu Allez, Xavier Roblin, Georgia Malamut, Cyriane Oeuvray, Nathalie Rolhion, Xavier Dray, Dominique Rainteau, Antonin Lamaziere, Emilie Gauliard, Julien Kirchgesner, Laurent Beaugerie, Philippe Seksik, Laurent Peyrin-Biroulet, Harry Sokol
Journal: Gut Microbes (2022)

Due to the potential role of the gut microbiota and bile acids in the pathogenesis of both inflammatory bowel disease (IBD) and sporadic colorectal cancer, we aimed to determine whether these factors were associated with colorectal cancer in IBD patients. 215 IBD patients and 51 non-IBD control subjects were enrolled from 10 French IBD centers between September 2011 and July 2018. Fecal samples were processed for bacterial 16S rRNA gene sequencing and bile acid profiling. Demographic, clinical, endoscopic, and histological outcomes were recorded. Characteristics of IBD patients included: median age: 41.6 (IQR 22); disease duration 13.2 (13.1); 47% female; 21.9% primary sclerosing cholangitis; 109 patients with Crohn's disease (CD); 106 patients with ulcerative colitis (UC). The prevalence of cancer was 2.8% (6/215: 1 CD; 5 UC), high-grade dysplasia 3.7% (8/215) and low-grade dysplasia 7.9% (17/215). Lachnospira was decreased in IBD patients with cancer, while Agathobacter was decreased and Escherichia-Shigella increased in UC patients with any neoplasia. Bile acids were not associated with cancer or neoplasia. Unsupervised clustering identified three gut microbiota clusters in IBD patients associated with bile acid composition and clinical features, including a higher risk of neoplasia in UC in two clusters when compared to the third (relative risk (RR) 4.07 (95% CI 1.6–10.3, P < .01) and 3.56 (95% CI 1.4–9.2, P < .01)). In this multicentre observational study, a limited number of taxa were associated with neoplasia and exploratory microbiota clusters co-associated with clinical features, including neoplasia risk in UC. Given the very small number of cancers, the robustness of these findings will require assessment and validation in future studies.
Factors associated to hospitalizations in older cancer patients treated with chemotherapy.
Authors: Claudia Bordignon, Daniela Dornelles Rosa
Journal: Journal of Clinical Oncology (2022)

e24025 Background: Chemotherapy toxicity (CT) is higher in elderly cancer patients, mainly due to fragilities identified in this subgroup. Hospitalization can be an adverse outcome of cancer treatment, which is disruptive in older patients, leading to worse functional status and cognitive disfunction, as well as increased costs for the health system. We evaluated patients treated with chemotherapy to identify hospitalizations related to oncological treatment and factors associated with this outcome. Methods: A retrospective study was conducted in a Brazilian Oncology Center. Patients ≥65 years old who started chemotherapy for solid tumors as curative or first-line therapy in 2019 were included and data was collected of the entire treatment until suspension or change in therapy (because of progression, completion, toxicity, or death). Those treated concomitantly with immunotherapy and radiotherapy were excluded. Characteristics of patients and their treatments were analyzed as risk factors for hospitalization through univariate analysis (UVA) with Fisher’s Exact Test and Mann-Whitney Test, and those variables considered significant (p &lt; 0.05) were submitted to a multivariate analysis (MVA) with Logistic Regression. Results: We included 124 patients with a median of 70 (65-93) years old and a median of 6 (1-26) cycles of chemotherapy completed. There were 67% of women, 42.8% had Charlson Comorbidity Index (CCI) ≥1; polypharmacy (≥5 medications) was present in 38.7%; the main cancer treated were gastrointestinal (34.7%), breast (21%) and pancreas/biliary tract (20.2%). Most patients had metastatic disease (54%) and received polychemotherapy (80.6%) as primary treatment ;body index measure was ≥25 in 50.8% and 24.2% lost 5% or more of body weight during the time analyzed. Unplanned hospitalizations occurred in 40 patients and 25 were considered associated with CT (febrile neutropenia, infections, gastrointestinal adverse events, worse renal function). In UVA, age, pancreas/ biliary tract cancers, CCI≥1 and polypharmacy were factors associated to hospitalization due to CT. After MVA, only CCI≥1 (OR 3.23, CI95%1.12 – 10.05) continued as an independent factor associated to CT. Conclusions: Evaluation of comorbidities with CCI can identify older patients at higher risk of hospitalization due to toxicity during treatment with chemotherapy. Comprehensive geriatric assessment should be offered to high-risk patients in order to develop strategies to prevent this adverse outcome.
HDL adverse remodelling and dysfunction is a temporal feature that can be reversed
Authors: L Schoch, P Sutelman, T Padro, L Badimon, G Vilahur
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministerio de Ciencia e Innovación (MCIN)/AEI/10.13039/501100011033 and Fondo Europeo de Desarrollo Regional (FFEDER) Background High-density lipoprotein (HDL) particles have been shown to undergo adverse remodelling and loss of function in the presence of comorbidities. It has been demonstrated that high low-density lipoprotein cholesterol (LDL-C) plasma levels induce compositional changes in HDL particles that render them dysfunctional. It is unknown, however, whether this HDL adverse remodelling is reversible. Purpose In this preclinical animal study we have investigated whether dyslipidaemia-induced HDL particle remodelling and dysfunction is a permanent adverse change or a temporal trait which can be regulated by dietary intervention. Methods After 10 days of high-fat diet (HFD) and reaching LDL-C levels of 392.8±94.9 mg/dL, the HDL particles of 15 pigs were characterized. Thereafter, pigs were randomly distributed into two arms. While group 1 was maintained on the same HFD (n=9), group 2 was switched to a normocholesterolemic diet (NCD; n=8) up to day 40. Blood was drawn at days 0 (baseline), 1, 3, 5, and 10 (to characterize HDL dysfunction over the 10-day period of dyslipidaemia induction), and at days 25 and 40 (to assess the HDL particle evolution in the intervention period). We assessed: a) HDL function [cholesterol efflux capacity (CEC) and antioxidant potential]; b) HDL particle number and size by nuclear magnetic resonance; c) oxidative susceptibility of LDL particles; d) HDL protein content of APOA-I, APOM, and APOC-III; and e) biochemical parameters. Results Up to day 10 there was a time-dependent increase in LDL-C levels that progressively induced the impairment of HDL CEC and antioxidant activity, higher HDL particle numbers, increased formation of conjugated dienes, and lower HDL-APOM content (p&amp;lt;0.01 vs baseline). All these parameters exhibited a plateau at day 10 and remained unchanged up to day 40 in those animals that were kept on HFD. Interestingly, in these animals a strong negative correlation was observed between HDL CEC and HDL-C levels (p&amp;lt;0.0001), with larger HDL particles being detected at day 40 (p&amp;lt;0.05 vs. baseline). On the contrary, all these parameters returned to physiological levels (baseline) in those animals that switched to a NCD (p=ns vs baseline). No changes were detected in APOA-I- and APOC-III- HDL content among animal groups and over time. Conclusion In the present study we evidence for the first time that dyslipidaemia-induced HDL particle remodelling and dysfunction is not a permanent adverse change. The implementation of a healthy dietary intervention acutely reverses HDL adverse remodelling and dysfunction in a preclinical animal model.
Planned and actual dose reduction of standard or modified FOLFIRINOX in metastatic pancreatic cancer: A systematic review and meta-analysis.
Authors: Kwangrok Jung, Su Hyun Choi, Jaihwan Kim, Jin-Hyeok Hwang, Jong-chan Lee
Journal: Journal of Clinical Oncology (2022)

e16279 Background: FOLFIRINOX showed high efficacy but also high toxicity in metastatic pancreatic cancer (MPC). To reduce toxicity and maintain efficacy, many kinds of studies on modified FOLFIRINOX have been conducted. However, these studies do not have unified pattern of dose-modification. In addition to the diversity of 'planned dose' in study design for modified FOLFIRINOX, the 'actually administered dose' for patients are much more diverse in the real world studies. We aimed to visualize 10 year trend of ‘planned’ and ‘actual’ dose of FOLFIRINOX in prospective and retrospective trials and investigate clinical outcomes according to dose modification. Methods: A systematic literature search of databases (Medline, Embase, and Scopus) between 1 January 2011 and 30 September 2021 was conducted. Eligible studies included patients treated with FOLFIRINOX as first-line treatment in MPC and reported any type of information in ‘planned’ and ‘actual’ dose of FOLFIRINOX. For evidence mapping sorted by four groups (table 1), a web-based and interactive bubble-plot program (www.RDI-map.com) was developed. For clinical outcome assessment, data on objective response rate (ORR) and hematologic toxicity rate were pooled with random-effect model and compared according to planned dose of FOLFIRINOX. Results: A total of 37 studies were identified for evidence mapping. In the mapping, ‘planned’ dose of FOLFIRINOX ranged with 75–100% for oxaliplatin, 75-100% for irinotecan, 0–100% for 5-fluorouracil (5FU)-push, and 75–133% for 5FU-continuous intravenous injection (CIV), respectively. The ‘actual’ dose of each agents went down to 54–96%, 61–88%, 0–92%, and 63–98%, respectively. In the pooled analysis with 27 studies including clinical outcome, the overall ORR was 30.9% (95% CI, 27.4-34.4%). Comparing planned ‘standard’ FOLFIRINOX with planned ‘modified’ regimen, the ORR was 28.2% [95% CI, 22.5-33.9%] and 33.8% [95% CI, 30.3-37.3%], respectively (P = 0.100). Febrile neutropenia was 11.6% [95% CI, 0-16.0%] and 5.5% [95% CI, 0-8.9%], respectively in the same order ( P = 0.030). Conclusions: The RDI-map.com effectively provided multifactorial evidence-mapping for the practical pattern of dose reduction in FOLFIRINOX, and it revealed a significant gap between ‘planned’ and ‘actual’ dose of FOLFIRINOX. Planned ‘modified’ FOLFIRINOX showed similar efficacy and reduced febrile neutropenia, compared to planned ‘standard’ regimen. This data can serve as a guidance in both prescribing FOLFIRINOX for clinicians and designing further studies for researchers in MPC. [Table: see text]
Humoral and cell-mediated immune response to the third dose of BNT162b2 anti-SARS-CoV-2 vaccine in patients with cancer on active treatment: Focus on wild type, Delta and Omicron strains.
Authors: Angioletta Lasagna, Irene Cassaniti, Federica Bergami, Daniele Lilleri, Elena Percivalle, Mattia Quaccini, Niccolò Alessio, Giuditta Comolli, Antonella Sarasini, Josè Camilla, Alessandro Ferrari, Francesca Arena, Simona Secondino, Daniela Cicognini, Roberta Schiavo, Giuliana Lo Cascio, Luigi Cavanna, Fausto Baldanti, Paolo Pedrazzoli
Journal: Journal of Clinical Oncology (2022)

e13505 Background: Although a full course of COVID-19 vaccine is effective in cancer patients, the duration of the protection and the efficacy of a booster dose against the new variants remain unknown. We prospectively evaluated the immunogenicity of the third dose of the SARS-CoV-2 BNT162b2 mRNA vaccine in cancer patients undergoing active treatment. Methods: Patients with solid cancer, vaccinated with a booster dose during active treatment, were prospectively enrolled in this study. Patients were classified in SARS-CoV-2 naïve (without previous COVID-19 infection) and SARS-CoV-2 experienced (with previous COVID-19 infection). Neutralizing antibody (NT Abs) titer and total anti-Spike IgG concentration were quantified in serum. Heparinized whole blood samples were used for SARS-CoV-2 Interferon Gamma Release Assay (IGRA). The primary endpoint was to assess the increase of IgG antibody level between baseline (T0) and 3 weeks after the booster (T1). Results: 142 consecutive patients were recruited. In SARS-CoV-2 naïve subjects, median level of IgG was 157 BAU/mL (interquartile range (IQR) 62-423) at T0 and reached median of 2080 (IQR 2080-2080) at three weeks after booster administration (T1; p &lt; 0.0001). A median 16-fold increase of SARS-CoV-2 NT Abs titre (IQR 4-32) was observed in naïve subjects (from median 20 IQR 10-40 to median 640 IQR 160-640; p &lt; 0.0001). Median IFN-γ level at T1 was significantly higher than that measured at T0 in SARS-CoV-2 naïve subjects (p = 0.0049) but not in SARS-CoV-2 experienced patients. No difference was observed in terms of median response between patients treated with immunotherapy and chemotherapy (p &gt; 0.05). A stronger correlation between SARS-CoV-2 NT Abs and total IgG level was observed at T0 (r = 0.76; p &lt; 0.0001) compared to T1 (r = 0.27, p = 0.0081). No correlation as regards the number of days was observed from the first to the third vaccination and SARS-CoV-2 NT Abs/total IgG. The median level of SARS-CoV-2 NT Abs was 32-fold lower against Omicron compared to wild type strain (p = 0.0004) and 12-fold lower compared to Delta strain (p = 0.0110). Conclusions: The third dose is able to trigger both the humoral and the cell-mediated immune response in cancer patients on active treatment. Our preliminary data about the neutralization of the SARS-CoV-2 vaccine against variants of concern (VOCs) seem to confirm the vaccine lower activity.